POS0951 BASELINE PREDICTORS OF SEVERE OUTCOMES IN IMMUNE CHECKPOINT INHIBITOR-INDUCED INFLAMMATORY ARTHRITIS
Authors: L. Cappelli, O. Kamal, C. Bingham, A. Shah
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Immune checkpoint inhibitor-induced inflammatory arthritis (ICI-IA) is the most common rheumatic adverse effect of cancer immunotherapy. Patients have dramatically different trajectories; some have a mild self-limited course, while others have severe IA requiring immunosuppression<sup>[1]</sup>. Additionally, some patients may have persistent IA beyond ICI cessation<sup>[1]</sup>. Risk factors for severe disease are unknown. <h3>Objectives</h3> To determine which clinical features at baseline rheumatology visit predict severe outcomes such as requirement of immunosuppression in ICI-IA. <h3>Methods</h3> Participants were drawn from a prospective longitudinal study of rheumatic immune related adverse events and had rheumatologist diagnosed ICI-IA. Demographics, cancer history and prior treatment, clinical (e.g.synovitis, tenosynovitis, inflammatory back pain determined by clinician) and laboratory features of arthritis and outcomes were collected at clinic visits. Descriptive statistics were calculated for demographic and clinical features of the whole cohort and for the two groups by primary outcome. The primary binary outcome was requirement of either csDMARDs and/or bDMARDs (determined by failure to wean to &lt; 10 mg prednisone/day); other outcomes were persistence of IA at least 6 months after ICI cessation and requirement of corticosteroids. T-tests or Wilcoxon rank sum tests and Fisher's exact tests were used to compare clinical characteristics by outcome categories. Logistic regression models evaluated univariate associations between clinical features and primary and secondary outcomes. Next, multivariable logistic regression was used to further evaluate these associations, adjusting for potential confounders. <h3>Results</h3> 126 patients with ICI-IA were included. The average age was 60; the majority were female (N=70 56%). The most common cancers were melanoma and lung cancer. Patients were primarily treated with anti-PD-(L)1 agents (N=78 62%) or combination anti-CTLA-4/PD-1 therapy (N=28 22%). Average clinical disease activity index (CDAI) was 17. Of the 126 patients, 53 (42%) required a csDMARD or bDMARD. In univariate logistic regression, higher baseline CDAI (OR 1.05 p=0.01) and presence of tenosynovitis (OR 4 p=0.005) were significantly associated with a higher likelihood of requiring DMARDs; there was a trend toward those treated with prior chemotherapy for cancer being less likely to need DMARDs for IA (OR 0.52 p=0.09). When adjusted for age, gender, and prior steroid use, tenosynovitis and higher CDAI remained associated with requiring DMARDs and prior chemotherapy was associated with lower likelihood of DMARDs (Table 1). Higher CDAI was also associated with higher likelihood of requiring corticosteroids (1.11 p=0.012). Those positive for rheumatoid factor had a lower likelihood of requiring steroids (0.168 p=0.013). Combination anti-CTLA-4/PD-1 (5.07 p=0.036) therapy and being on steroids at baseline (5.28 p=0.031) were associated with a higher likelihood of persistent IA; there were trends for higher CDAI and tenosynovitis associating with persistence. <h3>Conclusion</h3> Higher levels of disease activity and having tenosynovitis were associated with a higher likelihood requiring immunosuppression beyond corticosteroids for ICI-IA while those treated previously with chemotherapy were less likely to require additional immunosuppression. The presence of risk factors for severe disease at baseline may indicate higher initial steroid dose or earlier adoption of immunosuppression to improve outcomes. <h3>Reference</h3> [1]Braaten TJ et al. Immune checkpoint inhibitor-induced inflammatory arthritis persists after immunotherapy cessation. Ann Rheum Dis. 2020 Mar;79(3):332-338. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> Laura Cappelli Grant/research support from: Bristol-Myers Squibb, Omer Kamal: None declared, Clifton Bingham Grant/research support from: Bristol-Myers Squibb, Ami Shah Grant/research support from: Kadmon Corporation, Eicos Sciences, Medpace LLC, Arena Pharmaceuticals.